On June 20, 2000, the US Food and Drug Administration (FDA) approved the use of growth hormone in children with genetically confirmed Prader-Willi syndrome and evidence of growth failure.
[8, 9, 10] A study by Bakker et al indicated that growth hormone therapy improves the health-related quality of life (HRQOL) in children with Prader-Willi syndrome. The study included annual HRQOL assessments over an 11-year period.
[52]

A prospective cohort study by Donze et al reported that in infants and toddlers with Prader-Willi syndrome who underwent 3 years of growth hormone therapy, mental and motor development tended to see a greater increase in patients who began treatment at a younger age and who had lower psychomotor development at baseline. Using the Bayley Scales of Infant Development II, the investigators also found that over the 3-year treatment course, mental development increased from a mean (standard error of the mean [SEM]) baseline value of 58.1% to 79.6%, while mean (SEM) motor development rose from 41.9% at baseline to 78.2%.
[53]

A study by Scheermeyer et al indicated that in infants (aged 2-12 mo) with Prader-Willi syndrome, the effects of low-dose growth hormone treatment (4.5 mg/m2/wk) on growth and development are comparable to those of higher-dose treatment (7 mg/m2/wk). Moreover, although IGF levels rose in response to the lower-dose therapy, the increase was not excessive, signaling that the lower-dose approach may decrease long-term treatment risks.
[54]

A double-blind, placebo-controlled, crossover study by Miller et al suggested that low-dose intranasal oxytocin therapy may reduce appetite drive in patients with Prader-Willi syndrome, as well as improve socialization, anxiety, and repetitive behaviors in these individuals.
[55]

Next:

Surgical Care

See the list below:

Patients with Prader-Willi syndrome may require surgical care for treatment of complications of obesity, treatment of cryptorchidism, and scoliosis intervention. They may require urgent surgical attention for abdominal issues. Because of the high pain tolerance and decreased ability to vomit, they may present late with symptoms of cholecystitis, appendicitis, or acute gastric dilation with risk for progression to necrosis.
[11, 12]

Tonsillectomy, adenoidectomy, or tracheostomy placement may be required in patients with obstructive sleep apnea.

Biliopancreatic diversion and gastric bypass surgery have been ineffective for long-term weight reduction.
[56, 57] Significant disruption in the enterohepatic circulation of bile acids may result in deficiencies of fat-soluble vitamins and steatorrhea with anal pruritus due to bile acids. Anal pruritus may exacerbate rectal-picking compulsions. Deficiencies of fat-soluble vitamins may exacerbate the following:

Osteoporosis (vitamin D)

Hypochromic anemia (vitamin E)

Hyporeflexia (vitamin E)

Spinocerebellar ataxia (vitamin E)

Coagulopathy (vitamin K)

Night blindness (vitamin A)

Enhanced susceptibility to infections (vitamin A)

Previous

Next:

Consultations

Patients with Prader-Willi syndrome may require the support of the following specialists:
[7]

Geneticist for initial diagnosis and counseling

Developmental pediatrician for stimulation programs

Endocrinologist for management of hypogonadism

Nutritionist for dietary counseling

Ophthalmologist for management of strabismus

Pulmonologist for management of sleep apnea

Psychiatrist, psychologist, or both for management of behavioral issues

Gastroenterologist for GI issues

Previous

Next:

Diet

Patients with Prader-Willi syndrome have hyperphagia (onset in children aged 1-6 y) and diminished basal metabolic rate. Various treatment modalities for weight control, ranging from behavioral modification to anorexic agents, have been largely unsuccessful in curbing hyperphagia. However, these modalities may yield some success when used at group home settings.
[7, 57]

Significant dietary restrictions are not implemented during early childhood to ensure optimal myelination.

Institution of a balanced hypocaloric diet (1000 calories with supplementation of vitamins and calcium) is generally implemented at early school age with careful monitoring by a dietitian.

As children with Prader-Willi syndrome become ambulatory, limitation of access to foods is essential for modulation of weight. Placement of locks on cupboards and refrigerators, use of smaller dishes, and restriction of access to food in the school environment help deter excessive weight gain.

In patients with morbid obesity, a protein-sparing modified fast with careful medical and nutritional supervision over several weeks may facilitate short-term weight loss.
[58]

Based on the feeding behaviors of patients with Prader-Willi syndrome, one study assessed laboratory changes, metabolic changes, and growth changes and identified a total of 7 different nutritional phases, with 5 main phases and subphases in phases 1 (poor feeding and failure to thrive in infancy) and 2 (hyperphagia leading to obesity in later childhood). The study shows that progression of the nutritional phases is much more complex than the previously recognized 2 nutritional stages; awareness of these phases may help develop therapies and prevent or delay the early onset of obesity.
[59]

Previous

Next:

Activity

See the list below:

Patients with Prader-Willi syndrome have hypotonia and require supplemental occupational and physical therapy to promote acquisition of gross and fine motor skills and to strengthen spinal musculature in order to minimize scoliosis.
[48]

Encouragement of physical activity at home, at school (eg, increased physical education periods), and in the community (eg, Special Olympics) is essential for modulation of weight.

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Alexion Pharmaceuticals, Ultragenyx Pharmaceutical, and Biomarin Pharmaceuticals<br/>Honoraria for: Alexion Pharmaceuticals, Biomarin Pharmaceuticals.

Michael Fasullo, PhD Senior Scientist, Ordway Research Institute; Associate Professor, State University of New York at Albany; Adjunct Associate Professor, Center for Immunology and Microbial Disease, Albany Medical College